Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity

Area of Science:

• Immunology
• Dermatology
• Autoimmunity

Background:

• Psoriasis is a T-cell mediated autoimmune skin disease.
• HLA-C*06:02 is a major genetic risk factor.
• Previous research identified an autoimmune response against melanocytes mediated by HLA-C*06:02 and an ADAMTSL5 epitope.

Purpose of the Study:

• Identify environmental antigens that trigger psoriasis autoimmunity.
• Investigate the role of T-cell receptor (TCR) polyspecificity in psoriasis pathogenesis.

Main Methods:

• Screened databases for environmental peptides activating a specific Vα3S1/Vβ13S1 TCR.
• Assessed peptide immunogenicity using lymphocyte stimulation and HLA-C*06:02 tetramers in psoriasis patients and controls.

Main Results:

• Identified activating peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens.
• Demonstrated that the same CD8+ T-cells can recognize both the autoantigen ADAMTSL5 and environmental antigens (e.g., wheat peptides).
• Observed that a wheat-free diet improved psoriasis in some patients.

Conclusions:

• TCR polyspecificity allows environmental antigens to trigger the psoriatic autoimmune response against melanocytes.
• Environmental risk factors may contribute to psoriasis development and progression.
• Avoiding specific environmental triggers could aid in psoriasis management.